期刊
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
卷 108, 期 1, 页码 -出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djv306
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资金
- Terapia Molecolare dei Tumori from Fondazione Oncologia Niguarda Onlus
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [9970]
- European Union Seventh Framework Programme [259015]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) IG grant [12812]
In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family of receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event in CRC that renders tumors sensitive to TRKA kinase inhibitors in preclinical models. We identified abnormal expression of the TRKA protein in tumor and liver metastases of a CRC patient refractory to standard therapy. Molecular characterization unveiled a novel LMNA-NTRK1 rearrangement within chromosome 1 with oncogenic potential, and the patient was treated with the pan-TRK inhibitor entrectinib, achieving partial response with decrease in hepatic target lesions from 6.8 and 8.2 cm in longest diameter to 4.7 and 4.3 cm, respectively. To our knowledge, this is the first clinical evidence of efficacy for therapeutic inhibition of TRKA in a solid tumor, illuminating a genomic-driven strategy to identify CRCs reliant on this oncogene to be clinically targeted with entrectinib.
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